Реакция #57989

Уравнение реакции

(2-Hydroxyethyl)carbamic acid tert-butyl ester

4-hydroxybenzoic acid methyl ester

diisopropyl azodicarboxylate

Acetyl Chloride

Triphenylphosphine

→

4-(2-aminoethoxy)benzoic acid methyl ester hydrochloride

Выход 93.5%

Растворители

tetrahydrofuran

tetrahydrofuran

Условия реакции

Обработка

1. 1
   Другоеthe reaction temperature below 10° C
2. 2
   workup.ADDITIONAfter addition
3. 3
   Температураto warm slowly to ambient temperature
4. 4
   ДругоеAfter completion of reaction, solvent
5. 5
   workup.DISTILLATIONwas distilled under reduced pressure
6. 6
   workup.DISSOLUTIONthe resulting oil was dissolved in ethanol (500 ml)
7. 7
   Другоеto rise to 40° C
8. 8
   workup.STIRRINGThe resulting suspension was stirred at 40° C. until completion of reaction
9. 9
   ДругоеAfter completion of reaction
10. 10
    Фильтрацияthe resulting crystals were filtered on a coarse frit
11. 11
    Промывкаwashed with ethyl Acetate (300 mL)
12. 12
    ДругоеThe material is dried in vacuo

Методика

(2-Hydroxyethyl)carbamic acid tert-butyl ester (152.0 g, 0.942 mol) and 4-hydroxybenzoic acid methyl ester (174.0 g, 1.12 mol) were dissolved in tetrahydrofuran (2000 ml) and cooled to 0-5° C. Triphenylphosphine (292.8 g 1.116 mol) was added to the cooled mixture. A solution of diisopropyl azodicarboxylate (246.0 g, 1.218 mol) in tetrahydrofuran (400 ml) was added dropwise over a period of one to two hours keeping the reaction temperature below 10° C. After addition, the reaction was allowed to warm slowly to ambient temperature and stirred overnight. After completion of reaction, solvent was distilled under reduced pressure and the resulting oil was dissolved in ethanol (500 ml) and ethyl acetate (2000 ml). Acetyl Chloride (222.0 g, 2.826 mol) was added drop wise over fifteen minutes with the temperature allowed to rise to 40° C. The resulting suspension was stirred at 40° C. until completion of reaction. After completion of reaction, the resulting crystals were filtered on a coarse frit and washed with ethyl Acetate (300 mL). The material is dried in vacuo to give of 4-(2-aminoethoxy)benzoic acid methyl ester hydrochloride (204.1 g) as a white crystalline solid.

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